A critical view on conservative mutations

By analysing the surface composition of a set of protein 3D structures, complemented with predicted surface compositional information for homologous proteins, we have found significant evidence for a layer composition of protein structures. In the innermost and outermost parts of proteins there is a...

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Veröffentlicht in:Protein engineering 2001-06, Vol.14 (6), p.397-402
Hauptverfasser: Jonson, Per Harald, Petersen, Steffen B.
Format: Artikel
Sprache:eng
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Zusammenfassung:By analysing the surface composition of a set of protein 3D structures, complemented with predicted surface compositional information for homologous proteins, we have found significant evidence for a layer composition of protein structures. In the innermost and outermost parts of proteins there is a net negative charge, while the middle has a net positive charge. In addition, our findings indicate that the concept of conservative mutation needs substantial revision, e.g. very different spatial preferences were found for glutamic acid and aspartic acid. The alanine screening often used in protein engineering projects involves the substitution of residues to alanine, based on the assumption that alanine is a `neutral' residue. However, alanine has a high negative correlation with all but the non-polar residues. We therefore propose the use of, for example, serine as a substitute for the residues that are negatively correlated with alanine.
ISSN:0269-2139
1741-0126
1460-213X
1741-0134
DOI:10.1093/protein/14.6.397